Purpose
Clinical trials transparency requires trial registration and the posting of results on a public register. US regulations also require the posting of protocols and statistical analysis plans ...(SAPs). For US Federal agency funded trials to be started on or after 21 January 2019, informed consent forms (ICFs) must also be posted. Posting these documents is not mandatory in other countries. We aimed to assess compliance with US regulations of trials conducted in the US or in other countries with respect to ICFs, protocols, SAPs, and results.
Methods
This cross-sectional analysis (27 April 2023) comprised completed medicines trials to be started on or after 21 January 2019 registered on ClinicalTrials.gov. Trial data were registered by funder type (i.e., ‘US federal agencies’, industry, and ‘all others’) and development phase.
Results
Of 5,584 trials, 40% were conducted solely in the US. 47% and 12% of US and non-US trials had posted results. Some 40% of US trials had posted protocols and SAPs as did 9% of trials conducted in other countries. Only 10% (US) and 2% (other countries) of trials had posted ICFs. When the margin of the last 2 and 12 months after primary completion date were considered in the analysis, ICF posting rate did not change, but posting results increased to 64% for US trials. ‘US Federal agencies’ funded trials were significantly more likely to post ICFs than industry OR 23.9 (12.5-45.7; <.001) or ‘all others’ OR 3.16 (1.79-5.56; <.001).
Conclusion
Future interventions should be considered to encourage timely posting of trial results and information.
We aim to characterize industry-funded trials that have posted the informed consent forms (ICFs), and to assess whether the role played by industry as ‘sponsor’ or ‘collaborator’ could impact several ...relevant variables. A cross-sectional study was conducted on ClinicalTrials.gov on all industry-funded trials registered on or before 25 February 2023. We registered types of intervention, current recruitment status, design, enrollment, and countries involved. For trials with special interest to potential participants and investigators and/or clinicians an analysis of the role played by industry as ‘sponsor’ or ‘collaborator’ was performed. Of 116,281 industry-funded trials registered, 741 (0.6%) had posted ICFs. Most of these trials were categorized as ‘completed’ (n = 408) or ‘terminated’ (n = 107). The review of a sample of 359 trials showed that most were on drugs and/or biologics (59%), were randomized (51%), conducted exclusively in the USA (72%), and had posted results (79%), protocols (92%), and statistical analysis plans (SAPs) (89%). Trials in which industry participated as ‘collaborator’ were significantly more likely to post ICFs when trials were in the ‘active, not recruiting’ phase (OR 4.70, 99.71% CI 1.59–13.9, p < 0.001) than industry-sponsored trials. This was also the case when assessing drugs/biologics (OR 2.64, 99.71% CI 1.25–5.58, p < 0.001). Conversely, companies acting as ‘sponsors’ were significantly more likely to post ICFs with trials assessing devices, radiation interventions and/or diagnostic tests (OR 0.37, 99.71% CI 0.17–0.79, p < 0.001) than when participating as ‘collaborators’. While industry-funded trials rarely post ICFs, when they do, they are highly compliant with transparency requirements. Regulations and ethics codes should consider requiring posting of protocols, SAPs, and ICFs for all clinical trials, regardless the type of sponsor.
Graphical Abstract
This study aimed to evaluate the bone microstructure to determine whether curative surgery of primary hyperparathyroidism produces changes in bone mineral density (BMD), trabecular bone score (TBS), ...and three-dimensional (3D) dual x-ray absorptiometry (DXA) parameters and whether these changes are comparable.
We retrospectively studied 85 patients (60 women and 25 men, 60.4 ± 12.5 years) diagnosed with primary hyperparathyroidism and undergoing parathyroidectomy. Mean percent changes in BMD (lumbar spine LS, femoral neck FN, total hip TH, and 1/3 radius), TBS and 3D-DXA parameters (trabecular volumetric BMD (vBMD), cortical vBMD, integral vBMD, cortical surface density (sBMD), and cortical thickness at TH) after surgery (12, 24, and/or 36 months) were calculated and compared, and we sought the determinants of these changes.
After parathyroidectomy, BMD presented statistically significant mean increases in LS, FN, and TH during the first 3 years after surgery (P < .001), accompanied by an improvement in all 3D-DXA parameters, but there were no significant changes in 1/3 radius BMD or TBS. Cortical sBMD, trabecular vBMD, and integral vBMD reached mean increases of similar magnitude to those of FN and TH BMD. Age and preoperative serum levels of parathyroid hormone and carboxy-terminal telopeptide of type 1 collagen were significantly associated with percent changes after surgery.
We found a benefit of parathyroidectomy for bone, with significant percent increases in LS, FN, and TH BMD up to the third year after surgery, and a qualitative benefit for the hip in both its trabecular and cortical compartments and bone strength.
•EU regulation requires posting clinical trial results on EudraCT, that will be publicly available on the EU-CTR, within 12 months of completion.•Among the five top non-commercial sponsors with at ...least five trials due to report by country, the UK-, Belgium- and Germany-based sponsors have reported more than 50% of the trials due to report. Spain, France and the Netherlands, reported between 4 and 21% of trials due to report.•Between 2018 and 2021, the 49 worst performers have a 806% increase in the number of trials reported. But still 10 non-commercial sponsors have failed to report any results.
To describe the trial results reporting behavior of leading European non-commercial sponsors by country and over time.
Cross-sectional analysis describing results reporting rates to the European Clinical Trials Registry among the top sponsors across Europe as of May 2021 and a comparison of reporting trends for a cohort of major sponsors between January 2018 and May 2021.
Fifty-nine highly active sponsors from 10 countries and 9 collaborative groups had 1,916 trials due to report, representing 14% of all due trials on the registry (n = 13,709); of these, 1,058 had reported results (55.2%). Sponsors in the UK, Belgium and Germany had the highest compliance at 94%, 69% and 58%; those in Spain, France and the Netherlands, had the lowest, ranging from 4% to 21%. Collaborative groups had a reporting rate of 50%. In the major sponsors cohort (n = 49), those with no reporting to the registry decreased from 27 (55%) in 2018 to 10 (20%) in 2021. Thirteen of these sponsors (27%) reached a 90-100% reporting rate in 2021 compared to 0 in 2018.
Compliance with EU regulations by non-commercial sponsors is highly variable between countries. Enforcement of EU reporting regulations should be prioritized.
Background
Asthma is a syndrome characterized by airway inflammation and obstruction. Due to its heterogeneity, the difficulties in asthma diagnosis and treatment make the discovery of new biomarkers ...a focus of research. So, we determined the differential miRNA expression of eosinophils between healthy and asthmatic patients and to establish a differentially expressed miRNA profile detectable in sera for use as biomarker.
Methods
MicroRNAs from peripheral eosinophils from healthy and asthmatic subjects were isolated and analyzed by next‐generation sequencing and confirmed by quantitative PCR in 29 asthmatics and 10 healthy individuals. The levels of serum miRNAs were performed by quantitative PCR in 138 asthmatics and 39 healthy subjects. Regression analysis and Random Forest models were performed.
Results
We found a set of miRNAs whose expression differs between eosinophils from asthmatics and healthy subjects. These miRNAs can classify asthmatics into two clusters that differed in the number of eosinophils and periostin concentration in serum. Some of these miRNAs were also confirmed in sera, as miR‐185‐5p which discriminates asthmatics from healthy subjects. Together with other two miRNAs, miR‐185‐5p allowed us to create a logistic regression model to discriminate better both conditions and a Random Forest model that can even sort the asthmatics into intermittent, mild persistent, moderate persistent, and severe persistent asthma.
Conclusion
Our data show that miRNAs profile in eosinophils can be used as asthma diagnosis biomarker in serum and that this profile is able to rank asthma severity.
Eosinophils from asthmatics present a different profile in microRNAs (miRNAs) compared to eosinophils from healthy subjects. As eosinophils obtention from patients is not a standardized method, we analyzed these miRNAs in serum showing that miRNAs profile expression in this biofluid can be used for asthma diagnosis and for severity classification.
Objectives
The rate of eosinophilic esophagitis (EoE) diagnosis is increasing. This study aims to determine the incidence of EoE in the pediatric population residing in the southwestern Madrid and to ...analyze whether absolute monthly pollen counts, modified or not by the principal atmospheric pollutants, are associated with it.
Methods
A cross‐sectional study on prospectively recruited patients was designed to calculate the incidence of EoE in children aged under 15 years who were diagnosed between September 2014 and August 2016 in twelve hospitals.
We collected demographic and symptoms data, date of onset of symptoms, date of medical consultation, and date of endoscopic diagnosis of each included patient. Relative risk estimation was performed to assess the association between the incidence of diagnosis and monthly pollen counts and levels of atmospheric pollutants. All these models were adjusted for the number of total patients that underwent endoscopy at first time.
Results
One hundred forty‐eight patients were included. The most frequent symptoms were abdominal pain 42.57%, dysphagia 42.57%, and impaction 39%–86%. The median overall monthly incidence was 1.13 interquartile rank: 0.97–1.43 cases/100,000 children, and the annual mean was 15.2. The overall analysis of the relationship between incidence and absolute monthly counts, corrected for the number of first‐time endoscopies performed, revealed no statistically significant association with pollen and air pollutants. There was a higher frequency of diagnosis during the pollination period of Cupressaceae relative risk 1.647; 95% CI (1.192–2.276) p < .002 and during February and November (relative risk 1.67; p < .01).
Conclusions
This study confirms the high incidence of eosinophilic esophagitis and also suggests a period of higher incidence of diagnosis in the months of February and November as well as in the period of high pollination of Cupressaceae.
Summary
Lumbar fractures and/or multiple fractures at the lumbar or thoracolumbar regions are risk factors for sagittal malalignment in patients older than 70 years old. Although patients with ...OVF show a huge capacity to compensate after the fractures, lumbar and TL lumbar fractures require closer monitoring.
Purpose
To assess the impact of osteoporotic vertebral fractures on the sagittal alignment of the elderly and identify risk factors for sagittal malalignment.
Methods
We performed a retrospective study on a cohort of 249 patients older than 70 years old and diagnosed with osteoporosis who suffered chronic vertebral fractures. Demographic and radiological data were collected. Full-spine lateral X-rays were obtained to analyze the sagittal plane. Patients were classified according to the number and location of the fractures. Pearson’s correlation coefficient was used to assess the relationships between the type of fractures and sagittal alignment.
Results
A total of 673 chronic fractures were detected in 249 patients with a mean number of vertebral fractures per patient of 2.7 ± 1.9. Patients were divided into 9 subgroups according to the location and the number of fractures. Surprisingly, any of the aggregated parameters used to assess sagittal alignment exceeded the threshold defined for malalignment. In the second part of the analysis, 41 patients with sagittal malalignment were identified. In this subpopulation, an overrepresentation of patients with lumbar fractures (34% vs. 11%) and an under-representation of thoracic fractures (9% vs. 34%) were reported. We also observed that patients with 3 or more lumbar or thoracolumbar fractures had an increased risk of sagittal malalignment.
Conclusions
Lumbar fractures and/or multiple fractures at the lumbar or thoracolumbar regions are risk factors for sagittal malalignment in patients older than 70 years old. Although patients show a remarkable capacity to compensate, fractures at the lumbar and thoracolumbar regions need closer monitoring.
Obstructive sleep apnea (OSA) has been linked to tumorigenesis and tumor progression.
The Sleep Apnea in Lung Cancer (SAIL) study (NCT02764866) was designed to determine the prevalence of OSA in ...patients with lung cancer.
Cross-sectional study including consecutive patients with newly diagnosed lung cancer. All patients were offered home sleep apnea testing (HSAT) and administered a sleep-specific questionnaire prior to initiating oncologic treatment. Sleep study-related variables, symptoms, and epidemiologic data as well as cancer related variables were recorded.
Eighty-three patients were enrolled in the SAIL study. Sixty-six completed HSAT. The mean age was 68 ± 11 years and 58% were male with a mean body mass index of 28.1 ± 5.4. Forty-seven percent were current smokers, 42% former smokers, and 11% never smokers with a median tobacco consumption of 51 pack-years. Fifty percent had COPD with a mean FEV1 of 83 ± 22.6% of predicted and a mean DLCO of 85.5 ± 20.1%. Adenocarcinoma was the most common histologic type (46.7%), followed by squamous cell (16.7%) and small cell (16.7%). Most patients were diagnosed at an advanced stage (65% in stages III-IV). The vast majority (80%) had OSA (apnea-hypopnea index AHI > 5), and 50% had moderate to severe OSA (AHI > 15) with a mean Epworth Sleepiness Score of 7.43 ± 3.85. Significant nocturnal hypoxemia was common (Median T90: 10.9% interquartile range 2.4-42.2).
Sleep apnea and nocturnal hypoxemia are highly prevalent in patients with lung cancer.
This study aims to investigate ultrasound (US) findings on salivary glands (SG) in patients with Sjögren syndrome (SS) vs. other connective tissue diseases (CTDs) and to assess the relationship of ...SGUS abnormalities with autoantibody profile in both groups. We enrolled 81 patients, 45 diagnosed with SS (39 with primary SS, 6 with secondary SS) and 36 diagnosed with other CTDs. All patients underwent a prospective evaluation of sicca symptoms, a Schirmer’s test, and a B-mode US assessment of the parotid and submandibular glands, all blinded to the diagnosis. Each SG was semi-quantitatively scored 0–3; a grade ≥ 2 was considered pathological. SGUS involvement was classified as normal or pathological at the patient level and for each pair at the gland level. In addition, a total SGUS score of 0–12 and a parotid/submandibular score of 0–6 were calculated for each patient. Autoimmunity laboratory data were also obtained. All SGUS scores were higher in SS patients than in those with CTD (
p
< 0.001) and significantly more SS patients showed a pathological global (
p
< 0.001), parotid (
p
< 0.001), or submandibular (
p
= 0.001) US score compared with CTD patients. In SS patients, the presence of autoantibodies was significantly associated with pathological SGUS and higher scores, particularly at the parotid level, while in CTD patients, xerostomia and a pathological Schirmer’s test were associated with pathological US and higher scores at the submandibular level (
p
< 0.05). SGUS showed a different grade of abnormality, site involvement, and associated autoantibody profile in SS patients as compared with other CTD.
Key Points
•
Patients with SS and other CTDs showed different grades of SGUS abnormality
.
•
Patients with SS and other CTDs showed different gland involvement and associated autoantibody profiles
.
•
Anti-Ro60 and anti-Ro52 Ro60 positivity were associated with the severity of parotid involvement in SS patients.
PDF
